Feasibility of a combined intermittent theta-burst stimulation and video game-based dexterity training in Parkinson's disease.

BACKGROUND: Persons with Parkinson's disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD. METHODS: A total of nine persons with PD (mean age 63.3 ± 8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session. RESULTS: Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55-97.5) and a significant Spearman's correlation with the Flow State Scale (r = .762, p = .017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT. CONCLUSION: This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial. Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021.

An Overview of Wearable Haptic Technologies and Their Performance in Virtual Object Exploration.

We often interact with our environment through manual handling of objects and exploration of their properties. Object properties (OP), such as texture, stiffness, size, shape, temperature, weight, and orientation provide necessary information to successfully perform interactions. The human haptic perception system plays a key role in this. As virtual reality (VR) has been a growing field of interest with many applications, adding haptic feedback to virtual experiences is another step towards more realistic virtual interactions. However, integrating haptics in a realistic manner, requires complex technological solutions and actual user-testing in virtual environments (VEs) for verification. This review provides a comprehensive overview of recent wearable haptic devices (HDs) categorized by the OP exploration for which they have been verified in a VE. We found 13 studies which specifically addressed user-testing of wearable HDs in healthy subjects. We map and discuss the different technological solutions for different OP exploration which are useful for the design of future haptic object interactions in VR, and provide future recommendations.

Validation of the Apraxia Screen TULIA (AST) in Schizophrenia.

INTRODUCTION: Deficits in social interaction and community functioning, including impaired use, performance, and perception of hand gestures, are key features in schizophrenia. A well-established tool to assess gesture deficits is the test of upper limb apraxia (TULIA). However, given its time-consuming application based on video analyses, research has proposed the bedside apraxia screen of TULIA (AST). This study aims to test the validity and reliability of the AST to detect gesture abnormalities at bedside in a sample of 27 patients diagnosed with schizophrenia, schizotypal disorder, acute and transient psychotic disorders, or schizoaffective disorder. METHODS: Patients completed the 48-item TULIA and the 12-item AST. Two different raters assessed the AST: one at bedside (online) and the other based on the video recordings. RESULTS: The total AST scores demonstrated a high parallel reliability, moderate inter-rater reliability on a single-item level, and good construct validities. CONCLUSIONS: The psychometric properties of the AST suggest it can well be used for the clinical assessment of gesture deficits in schizophrenia. However, when detailed information is required, the AST rated from video or conducting the full TULIA is recommended. The findings call for refining the selection of the TULIA items for a psychosis-AST bedside test to increase specificity.

Theta burst stimulation in neglect after stroke: functional outcome and response variability origins.

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome.

Exergaming-Based Dexterity Training in Persons With Parkinson Disease: A Pilot Feasibility Study.

BACKGROUND AND PURPOSE: Many individuals with Parkinson disease (PD) suffer from impaired dexterity, which impacts activities of daily living and quality of life. Exergaming, video game-based training with augmented virtual reality, may have value for improving function. The aim of the present pilot study was to comprehensively evaluate the feasibility of a dexterity training program using exergaming, in individuals with PD. METHODS: Ten participants with PD (aged between 55 and 75 years, Hoehn and Yahr stages II-IV) trained over a period of 4 weeks, twice a week for 30 minutes. Baseline (T0) and postintervention (T1) assessments were done. Primary outcomes with respect to feasibility were the adherence rate, open-end questions, the level of participation (Pittsburgh Rehabilitation Participation Scale), and the usability (System Usability Scale). Dexterous function was measured with the Nine-Hole Peg Test and the Dexterity Questionnaire-24. Upper limb motor impairment was assessed by a modified version of the Movement Disorders Society Unified Parkinson's Disease Rating Scale III. Finally, quality of life was assessed by the 39-item Parkinson's Disease Questionnaire (PDQ-39). RESULTS: Adherence rate was 99%, motivation increased significantly from 3.9 to 4.8 (Pittsburgh Rehabilitation Participation Scale, P = 0.03), and system usability of the exergaming system was acceptable to very good. Regarding potential efficacy, participants with impaired dexterity at T0 significantly improved in the Nine-Hole Peg Test and the PDQ-39. DISCUSSIONS AND CONCLUSIONS: The outcomes of this pilot study suggest that exergaming is feasible and has potential to improve dexterity in individuals with PD. Its efficacy should be investigated in a properly powered randomized controlled trial.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A270).

Comprehensive ADL Outcome Measurement after Stroke: Rasch Validation of the Lucerne ICF-Based Multidisciplinary Observation Scale (LIMOS).

OBJECTIVE: To establish Rasch validation of the Lucerne International Classification of Functioning, Disability and Health (ICF)-based Multidisciplinary Observation Scale (LIMOS) in stroke. LIMOS measures the level of assistance in daily life activities related to motor function, communication, cognition, and domestic life. Rasch Measurement Theory (RMT) transforms an ordinal scale into an interval scale and thus the Rasch-based LIMOS scale captures a more accurate improvement of functional outcomes via Rasch-transformed scores. DESIGN: Cross-sectional study design. SETTING: Neurorehabilitation center, Luzerne, Switzerland. PARTICIPANTS: We recruited participants with stroke (N=407; age=63.2±16.0y; n=157 women) through consecutive sampling. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were assessed with LIMOS at admission and discharge of rehabilitation. We used RMT to evaluate overall model fit, response dependency, floor and ceiling effect, reliability, and differential item functioning (DIF) for sex, age, type, and time of stroke on the 4 LIMOS subscales using the Rasch Unidimensional Measurement Model (RUMM) 2030 program. RESULTS: The Rasch-based LIMOS subscales fit the Rasch model after reducing and rescoring items: motor (from 20 to 18 items), communication (5 items), cognition (from 15 to 13 items), and domestic life (5 items). There was no floor or ceiling effect. Some artificial DIF was identified. Scoring at discharge was dependent on the scoring responses at admission, which means that without applying a correction factor to the discharge scores, there was an underestimation of change in scores between admission and discharge, ranging from 0.24 to 0.97 logits (10.79%-49.24%) on the different subscales. CONCLUSIONS: The Rasch-based LIMOS scale is recommended to measure functional outcome in people with acute or chronic stages of ischemic or hemorrhagic stroke.

Long-Term Home-Monitoring Sensor Technology in Patients with Parkinson's Disease-Acceptance and Adherence.

Parkinson's disease (PD) is characterized by a highly individual disease-profile as well as fluctuating symptoms. Consequently, 24-h home monitoring in a real-world environment would be an ideal solution for precise symptom diagnostics. In recent years, small lightweight sensors which have assisted in objective, reliable analysis of motor symptoms have attracted a lot of attention. While technical advances are important, patient acceptance of such new systems is just as crucial to increase long-term adherence. So far, there has been a lack of long-term evaluations of PD-patient sensor adherence and acceptance. In a pilot study of PD patients (N = 4), adherence (wearing time) and acceptance (questionnaires) of a multi-part sensor set was evaluated over a 4-week timespan. The evaluated sensor set consisted of 3 body-worn sensors and 7 at-home installed ambient sensors. After one month of continuous monitoring, the overall system usability scale (SUS)-questionnaire score was 71.5%, with an average acceptance score of 87% for the body-worn sensors and 100% for the ambient sensors. On average, sensors were worn 15 h and 4 min per day. All patients reported strong preferences of the sensor set over manual self-reporting methods. Our results coincide with measured high adherence and acceptance rate of similar short-term studies and extend them to long-term monitoring.

Deficient supplementary motor area at rest: Neural basis of limb kinetic deficits in Parkinson's disease.

Parkinson's disease (PD) patients frequently suffer from limb kinetic apraxia (LKA) affecting quality of life. LKA denotes an impairment of precise and independent finger movements beyond bradykinesia, which is reliably assessed by coin rotation (CR) task. BOLD fMRI detected activation of a left inferior parietal-premotor praxis network in PD during CR. Here, we explored which network site is most critical for LKA using arterial spin labeling (ASL). Based on a hierarchical model, we hypothesized that LKA would predominantly affect the functional integrity of premotor areas including supplementary motor areas (SMA). Furthermore, we suspected that for praxis function with higher demand on temporal-spatial processing such as gesturing, inferior parietal lobule (IPL) upstream to premotor areas would be essential. A total of 21 PD patients and 20 healthy controls underwent ASL acquisition during rest. Behavioral assessment outside the scanner involved the CR, finger tapping task, and the test of upper limb apraxia (TULIA). Whole-brain analysis of activity at rest showed a significant reduction of CR-related perfusion in the left SMA of PD. Furthermore, the positive correlation between SMA perfusion and CR, seen in controls, was lost in patients. By contrast, TULIA was significantly associated with the perfusion of left IPL in both patients and controls. In conclusion, the findings suggest that LKA in PD are linked to an intrinsic disruption of the left SMA function, which may only be overcome by compensatory network activation. In addition, gestural performance relies on IPL which remains available for functional recruitment in early PD.

White matter correlates of the disorganized speech dimension in schizophrenia.

Disorganized speech is related to functional abnormalities in schizophrenia. To test the association between formal thought disorders (FTDs) and white matter microstructure, we applied a behavioral rating and diffusion tensor imaging in 61 patients with schizophrenia spectrum disorders. The Bern Psychopathology Scale was used to rate the dimension of language abnormalities ranging from negative FTDs, basically unaltered speech, to positive FTDs. Tract-based spatial statistics indicated increased fractional anisotropy in left hemispheric pathways of the language system in patients with negative FTDs. Thus, altered white matter properties in relevant fiber tracts may represent vulnerability to specific formal thought disorders.

Spatial Neglect Predicts Upper Limb Use in the Activities of Daily Living.

BACKGROUND AND PURPOSE: Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL. METHODS: Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment. RESULTS: Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later. CONCLUSIONS: This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients.

Eye Gaze Behavior at Turn Transition: How Aphasic Patients Process Speakers' Turns during Video Observation.

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.

Repeated Intravenous Thrombolysis for Early Recurrent Stroke: Challenging the Exclusion Criterion.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) within 4.5 hours from symptom onset improves functional outcome in patients with acute ischemic stroke. Its use in patients with previous stroke within the preceding 3 months is contraindicated because of the assumed higher risk of intracranial hemorrhage. In addition, tissue-type plasminogen activator may itself promote neurotoxicity and blood-brain barrier disruption. However, safety and effectiveness of repeated IVT is essentially unknown in patients with early (<3 months) recurrent stroke (ERS), because they were excluded from thrombolysis trials. This article reports the largest case series of repeated IVT in ERS. METHODS: We reviewed databases of prospectively collected patient data of 8 European stroke centers for the presence of patients with ERS, who received IVT for both the index stroke and ERS. Demographics, clinical and radiological data, bleeding complications, and functional outcome were analyzed. RESULTS: We identified 19 subjects with repeated IVT in ERS. Mean age was 68±12 years, and 37% of them were female. Median interthrombolysis interval was 30 days (interquartile range, 13-50). Functional independence (modified Rankin scale score ≤2) was achieved in 79% of patients after the first and in 47.4% after repeated IV tissue-type plasminogen activator, respectively. There was no symptomatic intracranial hemorrhage. Median final infarct volume after the first IVT was 1.5 cm(3) (interquartile range, 0.5-3.1). CONCLUSIONS: Patients with small infarct volumes and robust clinical improvement might be considered for repeated IVT within 3 months. Studies following strict protocols and larger registries incorporating these patients might serve to identify selection criteria for the safe use of repeated IVT in ERS.

Theta burst stimulation over premotor cortex in Parkinson's disease: an explorative study on manual dexterity.

Dorsal pre-motor cortex (PMd) is thought to play a role in fine motor control. The aim of the present study was to investigate whether inhibitory or excitatory stimulation of PMd would have an impact on manual dexterity in Parkinson's disease (PD). Fifteen patients with PD participated in this study. High resolution structural MRI was used for neuro-navigated TBS. Participants were targeted with one train of TBS in three experimental sessions: sham stimulation over vertex, continuous TBS (cTBS) over PMd and intermittent TBS (iTBS) over PMd, respectively. Dexterity was measured by a coin rotation task (CRT), which is a valid measure to detect limb kinetic apraxia (LKA). Neither cTBS or iTBS significantly interfered with CRT. Post hoc sub-analysis in a group of PD patients (n = 5) with stronger baseline impairment, indicating LKA, revealed further deterioration of dexterous performance for the cTBS condition (p = 0.04). This sham controlled pilot study demonstrates that TBS over PMd does not significantly interfere with dexterity in PD. However, patients with dexterous impairment qualifying for LKA may be more susceptible to TBS.

Gesture Performance in First- and Multiple-Episode Patients with Schizophrenia Spectrum Disorders.

BACKGROUND/AIM: Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. METHODS: In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. RESULTS: Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. CONCLUSIONS: Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course.

Home-based training to improve manual dexterity in patients with multiple sclerosis: A randomized controlled trial.

BACKGROUND: Impaired manual dexterity is frequent and disabling in patients with multiple sclerosis (MS), affecting activities of daily living (ADL) and quality of life. OBJECTIVE: We aimed to evaluate the effectiveness of a standardized, home-based training program to improve manual dexterity and dexterity-related ADL in MS patients. METHODS: This was a randomized, rater-blinded controlled trial. Thirty-nine MS patients acknowledging impaired manual dexterity and having a pathological Coin Rotation Task (CRT), Nine Hole Peg Test (9HPT) or both were randomized 1:1 into two standardized training programs, the dexterity training program and the theraband training program. Patients trained five days per week in both programs over a period of 4 weeks. Primary outcome measures performed at baseline and after 4 weeks were the CRT, 9HPT and a dexterous-related ADL questionnaire. Secondary outcome measures were the Chedoke Arm and Hand Activity Inventory (CAHAI-8) and the JAMAR test. RESULTS: The dexterity training program resulted in significant improvements in almost all outcome measures at study end compared with baseline. The theraband training program resulted in mostly non-significant improvements. CONCLUSION: The home-based dexterity training program significantly improved manual dexterity and dexterity-related ADL in moderately disabled MS patients. Trial Registration NCT01507636.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect.

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Limb apraxia in multiple sclerosis: prevalence and impact on manual dexterity and activities of daily living.

OBJECTIVE: To evaluate the prevalence and impact of limb apraxia on manual dexterity and activities of daily living (ADLs) in patients with multiple sclerosis (MS). DESIGN: Survey. SETTING: University hospital. PARTICIPANTS: Consecutive patients (N=76) with clinically isolated syndrome, relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) or primary progressive multiple sclerosis (PPMS), Expanded Disability Status Scale (EDSS) score from 0 to 6.5, and aged from 18 to 70 years were included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Apraxia was assessed by the apraxia screen of TULIA (AST). The relationship of apraxia with ADLs and manual dexterity was evaluated using a dexterity questionnaire and the coin rotation task, respectively. RESULTS: Overall, limb apraxia was found in 26.3% of patients (mean AST score ± SD, 7.3±1.3; cutoff <9). Apraxia was significantly correlated with higher EDSS scores, longer disease duration, and higher age with the EDSS being predictive. Furthermore, patients with SPMS and PPMS were more apraxic than patients with RRMS. Finally, limb apraxia was significantly associated with impaired ADLs and manual dexterity. CONCLUSIONS: Limb apraxia is a frequent and clinically significant symptom contributing to disability in MS. It should therefore be evaluated and possibly treated, particularly in patients with MS reporting manual difficulties in everyday life.

Neurological Soft Signs Are Associated With Altered White Matter in Patients With Schizophrenia.

Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.

Improved gesturing in left-hemispheric stroke by right inferior parietal theta burst stimulation.

Objectives: Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation. Materials and methods: Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model. Results: Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R. Conclusion: One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.

Combining Repetitive Transcranial Magnetic Stimulation and Video Game-Based Training to Improve Dexterity in Parkinson's Disease: Study Protocol of a Randomized Controlled Trial.

Introduction: Patients with Parkinson's disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL) due to dysfunctional supplementary motor area (SMA). The aim of this clinical trial protocol work is to describe how the effectiveness of a combined repetitive transcranial magnetic stimulation (rTMS) over SMA and video-game-based skill training (VBT) in PD will be evaluated. The short and long-term benefits are assessed. Methods and analysis: A single-blind (patients) stratified (based on Hoehn & Yahr) parallel randomized sham-controlled rTMS-VBT study with a baseline and two follow-up measurements (3 and 12 weeks) is being conducted. These measurements include the dexterity questionnaire 24 (DextQ-24) as a primary outcome, and nine hole peg test and coin rotation task as main secondary dexterity outcomes. Further secondary outcomes will be the subscale II of the movement disorders society unified PD rating scale (MDS-UPDRS) to assess improvements on overall ADL and the Parkinson's Disease Questionnaire-39 to assess quality of life. Thirty-six outpatients (from one neurorehabilitation center) with PD (diagnosis based on brain bank criteria) will be recruited who report difficulties with dexterity in performing ADL. All PD patients will receive a 45-min VBT three times a week for 3 weeks. The PD patients randomized in the experimental group will receive VBT preceded by real rTMS, being intermittent theta burst (iTBS) stimulation sessions. The PD patients randomized to the control group receive a VBT with sham rTMS. Discussion: The study will provide evidence to determine whether a combined iTBS and VBT skill intervention is more effective than a VBT intervention alone to improve dexterity in PD. Ethics and dissemination: The study was approved by the Ethics Committee for Northwest and Central Switzerland (EKNZ), Switzerland 2019-00433. The study will be conducted in accordance with the Helsinki Declaration and the Guidelines of Good Clinical Practice. Informed consent will be signed prior to subject enrolment. Dissemination will include submission to international peer-reviewed professional journals and presentation at international congresses. The study protocol has been registered in the clinicaltrials.gov registry with the identification code: NCT04699149.